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Risk factors associated with the development of necrotizing enterocolitis in preterm infants on an exclusive human milk diet: a single-center case-control study

Abstract

Objective

Identify early neonatal and maternal risk factors for development of necrotizing enterocolitis (NEC) in preterm infants receiving an exclusive human milk diet (EHMD).

Study design

Preterm infants who developed NEC stage ≥2 while receiving an EHMD were compared to matched controls who did not develop NEC on the same diet. Predictors of NEC were selected for multiple-predictor logistic regression analysis based on literature or significance in single-predictor models.

Results

A total of 27 cases and 98 controls (mean GA = 27 weeks) were included. Groups did not differ significantly on baseline characteristics. Maternal urinary tract infection, maternal neutrophil-to-lymphocyte ratio before delivery, and vasopressor use during the first week significantly predicted NEC.

Conclusion

Despite the use of EHMD, NEC remains a concern, underlining its multifactorial nature. Results highlight the potential role of maternal inflammation and early neonatal hemodynamic instability in NEC development. Findings could inform future research aimed at identifying high-risk infants.

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Fig. 1: Combined logistic regression likelihood of necrotizing enterocolitis (NEC).

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

Authors

Contributions

Haider Ailumerab contributed to the conceptualization of the project, data collection, contributed to data analysis, and drafted the initial manuscript. Jamie Miller provided guidance on pharmaceutical aspects of the study and assisted with writing, critically reviewing, and revising the manuscript. Lise DeShea advised on statistical analyses, oversaw the database and secure data storage, analyzed the data, and assisted with writing and revising the manuscript. William Howard Beasley advised on statistical analyses, analyzed the data, created data visualizations, and assisted with writing the manuscript. Hala Chaaban contributed to the conceptualization, methodology, and data analysis, and provided critical revisions of the manuscript. Erynn M. Bergner contributed to the conceptualization and methodology, supervision of the project, and critically revised the manuscript. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

Corresponding author

Correspondence to Erynn M. Bergner.

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Competing interests

The authors have no conflicts of interest relevant to this article to disclose. EMB previously served as the Site PI for Prolacta Biosciences® unrelated trial on infants with congenital bowel disorders (2019-2023) for which the institution received research support. The other authors have no conflicts of interest to disclose.

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Ailumerab, H., Miller, J.L., DeShea, L. et al. Risk factors associated with the development of necrotizing enterocolitis in preterm infants on an exclusive human milk diet: a single-center case-control study. J Perinatol (2025). https://doi.org/10.1038/s41372-025-02401-2

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